Bismuth biokinetics and kidney histopathology after bismuth overdose in rats

• Published in: Archives of toxicology Vol. 74; no. 7; pp. 349 - 355
• Main Authors: LEUSSINK, Berend T, SLIKKERVEER, Anja, KRAUWINKEL, Walter J. J, VAN DER VOET, Gijsbert B, DE HEER, Emile, DE WOLFF, Frederik A, BRUIJN, Jan A
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2000
• Subjects: Absorption; Animals; Anti-Ulcer Agents - toxicity; Biological and medical sciences; bismuth; Bismuth - pharmacokinetics; Blood Glucose - drug effects; Creatinine - blood; Drug intoxications. Doping; Epithelial Cells - drug effects; Epithelial Cells - pathology; Female; Half-Life; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - pathology; Medical sciences; Necrosis; Organometallic Compounds - toxicity; Pharmacology. Drug treatments; Rats; Rats, Wistar; Toxicity Tests, Acute; Vacuoles - drug effects; Vacuoles - pathology; Kidney disease; Urinary system disease; Rat; Toxicity; Drug intoxication; Overdosing; Rodentia; Single dose; Oral administration; Antiulcer agent; Vertebrata; Renal tubule; Mammalia; Histopathology; Animal; Bismuth subcitrate; Pharmacokinetics; Antiacid
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040000150

Bismuth induced nephrotoxicity has been reported to occur after acute overdoses of Bi-containing therapeutic drugs. We studied the development of bismuth induced nephropathy and bismuth biokinetics in rats. Bismuth nephropathy was induced in 33 young adult female Wistar rats weighing ca. 175 g by feeding them a single overdose of colloidal bismuth subcitrate containing 3.0 mmol Bi/kg at (t = 0). Control animals (n = 7) were fed the vehicle only. The animals were sacrificed after 1-48 h. Plasma creatinine increased from 51 +/- 6 micromol/l at t = 0 to 550 +/- 250 micromol/l after 48 h in the experimental group. The S3 segment of the proximal tubule showed epithelial cell vacuolation after 1 h and necrosis after 3 h. Cells of the S1/S2 segment demonstrated vacuolation after 6 h and necrosis after 12 h. Biokinetics of bismuth in blood could best be described with a one-compartment model characterized by an absorption half-life of 0.32 h and an elimination halflife of 16 h. The peak concentration of about 7.0 mg Bi/l was reached after 2 h. In conclusion, cells of the S3 segment of the proximal tubule necrotized first after an oral colloidal bismuth subcitrate overdose and biokinetics of Bi in blood was best described by a one-compartment model.